TRABD2A promotes osteogenic differentiation of human periodontal ligament stem cells by modulating TNF-α and IL-1β

Background: Periodontitis is a chronic inflammatory condition characterized by destruction of periodontal support tissues and dysregulated immune responses, particularly involving cytokines like tumor necrosis factor-alpha (TNF-α) and interleukin-1 beta (IL-1β). Identifying molecules that regulate both inflammation and tissue regeneration is essential for targeted therapies. Following preliminary transcriptomic evidence on periodontal tissues, this study aimed to define the specific immunomodulatory and osteogenic regulatory effects of TRAB domain-containing protein 2A (TRABD2A).

Methods: RNA Sequencing was performed on periodontal tissues from patients with periodontitis and periodontally healthy individuals to identify differentially expressed genes and conduct functional enrichment analysis. TRABD2A expression and its effects on cell proliferation, inflammation, osteogenic markers expression, and mineralization were assessed in human periodontal ligament stem cells (hPDLSCs) treated with recombinant TRABD2A, Porphyromonas gingivalis lipopolysaccharide (LPS), or a TRABD2A inhibitor (o-Phenanthroline).

Results: RNA Sequencing revealed significant TRABD2A upregulation in periodontitis tissues, along with elevated bone-related genes runt-related transcription factor 2 (RUNX2) and receptor activator of nuclear factor-κB Ligand (RANKL) expression. In vitro experiments demonstrated that TRABD2A reduced the secretion of tumor necrosis factor-alpha (TNF-α) and interleukin-1 beta (IL-1β) and promoted the proliferation of hPDLSCs. Furthermore, TRABD2A upregulated RUNX2 expression and suppressed RANKL expression, while Alizarin Red staining results further confirmed its role in promoting osteogenic differentiation. The underlying mechanism may be associated with the enhancement of β-catenin expression.

Conclusion: TRABD2A exerts dual functions by promoting osteogenic differentiation and modulating inflammatory responses, highlighting its potential as an immunoregulatory and pro-regenerative target for periodontitis treatment.